Our laboratory has focused on factors that influence host responses to tumors and may adversely influence responses to immunotherapy. The expression of tumor associated antigens by autologous human primary and metastatic sarcomas has been clearly defined using a panel of monoclonal antibodies. It has been demonstrated that primary tumors and their metastases express similar antigens but almost invariably, micro-heterogeneity of tumor antigen expression results from antigen absent populations of cells within each tumor. The mechanism of heterogeneity for tumor antigen expression of the B16 melanoma system has been defined using a tumor specific monoclonal antibody. Variation in antigen expression correlated with variations of tumor cell density in culture. Monoclonal antibodies have been produced that recognize antigens newly expressed by NIH 3T3 firbroblasts transfected with oncogenes from human tumors. TWhese experiments define a new technique for the production of anti-tumor monoclonal antibodies and will also be useful in defining the mechanism of oncogene-related transformation. Two monoclonal antibodies have been produced and both are selective for human tumors. Conjugation to the A chain of ricin has produced a potent immunotoxin.